| Hypoxic-ischemic brain damage(HIBD) is a severe complication caused by asphyxia in newborn infants. At present, HIBD is still a major cause of perinatal death of newborn infants and permanent nervous system sequela such as cerebral palsy, epilepsy, neurodevelopmental retardation and learning disability of those who survived. However, there still isn't sufficiently effective treatment for HIBD due to the complicated pathogenesis. In recent years, moderate hypothermia (to reduce the brain temperature to 2-6℃) has been receiving more attention for it's prominent therapeutical effect and minor side-effects. Notwithstanding that animal experiments have shown the 72 hour post-ischemic moderate hypothermia had better therapeutical effects on HIBD, and that this treament has proven to be effective in clinical studies, the mechanism of of moderate hyphothermia is still not well-understood. The mechanisms of this treatment on HIBD may affect many aspects of the onset of the illness such as the reduction of the cerebral oxygen metabolic rate, the improvement of cellular energy metabolism, the inhibitation of the occurrence of apoptosis, the inhibitation of the process of cytotoxicity and the relief of the cerebral edema. Especially of interests is the variation of the energy metabalism in brain tissue during the treament process since the brain requires vast quantity of glucose supply directly from the blood stream without any reserve of its own. This study is based on the axis of the metabolism of glucose in the brain, analyzing the funtional indices of energy metabolism such as the variations of glucose quantities, of quantiies of ATP, and of the functions of mitochondrial in the brain under hypoxic and moderate hypothermia conditions, the changes in the morphometry of mitochodrial, the variation of of the glucose carrier, and the relationships and meaning among them.Part One The Effects of Moderate Hypothermia on the Cerebral Glucose Metabolism and the Functions of Mitochondria in Immature Rats with Hypoxic-Ischemic Brain DamagesMethods Seven-day-old Sprague-Dawley rat pups were subjected to unilateral ligation of the left carotid artery followed by exposure to hypoxia in 8% O2 for 2 hours, creating the model rats of hypoxic-ischemic brain damages. And then the model rats were randomly divided into normothermic recovered group (rectal temperature [RT]= 37℃, IN group) and moderate-hypothermic recovered group (RT = 32℃, IH group). Sham-operated rat pups in the same litter were control groups (normothermic control group, NC group, and moderate-hypothermic control group, HC group). At zero, 2, 6, 24, 48, and 72h after the end of hypoxic-ischemic (HI) insult, the ipsilateral brains were dissected and homogenized to measure glucose and ATP volume; and brain tissue were extracted to obtain mitochondria by density-centrifugation and speed-centrifugation for SDH activity, complex II activity and the capacity of ATP synthesization assay. Results For IN group, the brain glucose at 0 h after the end of HI was significantly lower than that of before HI. Two hours after the end of HI, the brain glucose recovered as normal and there was no significant change among all the groups；The brain ATP and brain-mitochondrial succinate dehydragenase (SDH)activity were initially decreased at 2 h, 6 h and then recovered gradually, it was at it's peak value at 72h but still lower than normal level obviously. Brain-mitochondrial complex II activity and the capacity of ATP synthesization were recovered at 2h, but they decreased again at 6 h, returning to normal level at 72h. For moderate-hypothermic group, ATP, SDH activity, complex II activity and the capacity of ATP synthesization were significantly higher in the IH groups at all the time points than those in IN groups. Conclusions These findings suggest that moderate hypothermia can inhibit the decrease of the mitochondrial SDH activity, mitochondrial complex II activity and the capacity of ATP synthesization, increase the brain ATP concentration, i...
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